Document Detail


Role of the cholesterol biosynthetic pathway in osteoblastic differentiation.
MedLine Citation:
PMID:  17721067     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cholesterol (C27H46O) is the principal structural lipid of the biological membrane, but it also plays an important role in many other biological functions. Even though the majority of body cholesterol is synthesized by the liver and secreted as circulating lipoproteins, many cell types can synthesize cholesterol ex novo. The biosynthetic pathway of cholesterol proceeds through several intermediates and involves different enzymes. The rate-limiting step of cholesterol synthesis is the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase that synthesizes mevalonate starting from HMG-CoA. Since natural inhibitors of HMG-CoA reductase, named statin, have been isolated, many others have been developed, which differ in their lipophilicity/ hydrophilicity. By using statins, many studies have been performed in order to shed light on the role of cholesterol on different cell types and, among these, on bone cells. In vivo studies have demonstrated that treatment of pluripotent mouse marrow stromal cells (M2-10B4) with statins inhibited the differentiation of these cells into osteoblastic cells, confirming the crucial role of cholesterol biosynthetic pathway for osteoblast differentiation. Conversely, other studies, using other cellular systems, have reported that statins may exert an anabolic effect on bone. Moreover, human and animal studies have shown that hypercholesterolemia may play an adverse effect in osteoporotic bone loss. In conclusion, it appears that cholesterol is important for different cellular activities, such as osteoblastic differentiation, if present in "normal" physiological concentration and particular experimental conditions, but it may exert adverse effects if present in excess.
Authors:
G Viccica; E Vignali; C Marcocci
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Journal of endocrinological investigation     Volume:  30     ISSN:  1720-8386     ISO Abbreviation:  J. Endocrinol. Invest.     Publication Date:  2007  
Date Detail:
Created Date:  2007-08-27     Completed Date:  2008-01-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7806594     Medline TA:  J Endocrinol Invest     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  8-12     Citation Subset:  IM    
Affiliation:
Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
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MeSH Terms
Descriptor/Qualifier:
Acyl Coenzyme A / metabolism
Animals
Cell Differentiation / physiology*
Cholesterol / biosynthesis*
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry,  metabolism
Molecular Structure
Osteoblasts / cytology,  physiology*
Osteogenesis / physiology
Chemical
Reg. No./Substance:
0/Acyl Coenzyme A; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 1553-55-5/3-hydroxy-3-methylglutaryl-coenzyme A; 57-88-5/Cholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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